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dc.contributor.author
Buil, Beatriz Achon
dc.contributor.author
Tackenberg, Christian
dc.contributor.author
Rust, Ruslan
dc.date.accessioned
2023-01-25T04:43:45Z
dc.date.available
2023-01-25T04:43:45Z
dc.date.issued
2022-11-18
dc.identifier.issn
0006-8950
dc.identifier.issn
1460-2156
dc.identifier.other
10.1093/brain/awac393
dc.identifier.uri
http://hdl.handle.net/20.500.11850/594617
dc.description.abstract
Stem cell therapy has been shown to improve stroke outcomes in animal models and is currently advancing towards clinical practice. However, uncertainty remains regarding the optimal route for cell delivery to the injured brain. Local intracerebral injections are effective in precisely delivering cells into the stroke cavity but carry the risk of damaging adjacent healthy tissue. Systemic endovascular injections, meanwhile, are minimally invasive, but most injected cells do not cross CNS barriers and become mechanically trapped in peripheral organs. Although the blood-brain barrier and the blood-CSF barrier tightly limit the entrance of cells and molecules into the brain parenchyma, immune cells can cross these barriers especially under pathological conditions, such as stroke. Deciphering the cell surface signature and the molecular mechanisms underlying this pathophysiological process holds promise for improving the targeted delivery of systemic injected cells to the injured brain. In this review, we describe experimental approaches that have already been developed in which (i) cells are either engineered to express cell surface proteins mimicking infiltrating immune cells; or (ii) cell grafts are preconditioned with hypoxia or incubated with pharmacological agents or cytokines. Modified cell grafts can be complemented with strategies to temporarily increase the permeability of the blood-brain barrier. Although these approaches could significantly enhance homing of stem cells into the injured brain, cell entrapment in off-target organs remains a non-negligible risk. Recent developments in safety-switch systems, which enable the precise elimination of transplanted cells on the administration of a drug, represent a promising strategy for selectively removing stem cells stuck in untargeted organs. In sum, the techniques described in this review hold great potential to substantially improve efficacy and safety of future cell therapies in stroke and may be relevant to other brain diseases.
dc.description.abstract
Achon Buil et al. review current developments in stem cell delivery after stroke with a focus on optimizing application routes. They summarize novel strategies including preconditioning, as well as genetic and pharmacological engineering of the cell graft before transplantation to facilitate crossing of the brain barriers.
dc.publisher
OXFORD UNIV PRESS
dc.subject
stroke
dc.subject
stem cells
dc.subject
brain shuttle
dc.subject
iPSC
dc.subject
BBB
dc.title
Editing a gateway for cell therapy across the blood-brain barrier
dc.type
Review Article
ethz.journal.title
Brain: A Journal of Neurology
ethz.journal.abbreviated
Brain
ethz.identifier.wos
ethz.publication.place
OXFORD
ethz.date.deposited
2023-01-25T04:43:46Z
ethz.source
WOS
ethz.rosetta.exportRequired
true
ethz.COinS
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